An environmentally friendly and mild Bischler cyclization was developed to access quinazolines with diverse substitution. Based on this method, a library of 53 quinazoline derivatives was prepared and tested in vitro for cytotoxicity and inhibition on T-cell and B-cell proliferation. Compounds 6b, 7b, 17b, 33, and 35 showed higher inhibitory activity on both T-cell and B-cell proliferations, with IC(50) values of 6.16, 6.30, 5.43, 2.54, and 9.80 μM on T-cell, respectively. All the tested compounds showed no obvious cytotoxicity at 10 μM concentration. The preliminary structure-activity relationship was concluded revealing that 4-position is the key modification site for potent quinazoline immunosuppressive agent.